Testosterone, like many anabolic steroids, was classified as a controlled substance in 1991. Testosterone is administered parenterally in normal and delayed-release (depot) forms. In September 1995, the FDA approved testosterone transdermal patches (Androderm), and many transdermal forms and brands are now available including implants, gels, and topical solutions. A testosterone buccal system, Striant, was FDA-approved in July 2003; Striant is a mucoadhesive product that adheres to the buccal mucosa and provides a controlled and sustained release of testosterone. In May 2014, the FDA approved an intranasal gel formulation of testosterone (Natesto). A transdermal patch (Intrinsa) for hormone replacement in women is under investigation; the daily dosages used in women are much lower than for products used in males. The FDA refused approval for Intrinsa in 2004 stating that more data regarding safety, especially in relation to cardiovascular and breast health, were required.
The preservative benzyl alcohol has been associated with serious adverse events, including the "gasping syndrome", and death in pediatric patients. Although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the "gasping syndrome", the minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the liver and kidneys' capacity to detoxify the chemical. Premature and low-birth weight infants may be more likely to develop toxicity.
Pharmaceutical companies have tried to develop hormonal male contraceptives with the intent of causing a withdrawal of the gonadotropin support to the testis with resultant suppression of spermatogenesis and ITT ( 14 ). Testosterone has been studied alone, as well as in combination with progestrogens ( 15 ). Testosterone used as a contraceptive agent may be used to determine the recovery of spermatogenesis after cessation of therapy. This analysis regarding the application of contraceptive studies to hypogonadal males is problematic. First, the men studied in contraceptive trials were not hypogonadal and did not have concerns about fertility. Many of these men had normal baseline testosterone levels, as well as sperm production. Additionally, different testosterone preparations and doses were used compared to clinical formulations.